The major objective of this study is to develop a comprehensive understanding of the keratinization process in order to more fully understand the numerous disorders which involve epidermis, hair and nails. Since the fibrous proteins play a key role in the keratinized tissues of man it is essential to obtain detailed information on their physicochemical properties. We plan to finish a rather complete study of prekeratin including its size, shape and polypeptide composition. The physicochemical properties of the polypeptides including amino acid composition, arrangement and configuration will be determined. This will be compared with the alpha-protein of stratum corneum to determine the changes which occur during the final stages of keratinization. This technique will then be applied to normal human stratum corneum and to certain inherited disorders of keratinization. The presence of additional cross-links in the fibrous proteins has been suggested but it remains to be shown if the epsilon-(gamma-glutamyl) lysine cross-link is present. An additional problem is the intracellular cement protein to which we have been given a lead by clinical studies on a keratolytic formulation. We are planning to develop techniques for studying the dynamic aspects of hair growth and to look more critically at the macromolecular components of hair including polymorphism of the alpha-polypeptides. We shall undertake comparative studies of the biophysical properties of prekeratin and the stratum alpha-protein in a number of vertebrate species to gain insight into variability in the keratinization process. Continued collection and study of inherited disorders of keratinization will be done and new therapeutic modalities will be developed and tested.